I hope to use myeloma-macrophage or other macrophage hybrid cell lines to increase our understanding of the role of the macrophage in the immune response and in the macrophage mediated killing of target cells. The specificity of Fc receptors for immunoglobulin will be studied using homogeneous antibodies from spleen-myeloma hybrids and constant region mutants. The structural determinants of antibodies which mediate macrophage effector functions will be examined. A major goal is to understand the macrophage-mediated suppression of both mitogenic and antigenic responses by lymphocytes and of antibody production in animals bearing myeloma tumors. Likewise the activation of macrophages by lymphokines will be studied. Variants of the cloned macrophage lines no longer capable of being induced to behave in specified ways or no longer capable of altering lymphocyte function will be sought and studied. It is hoped that studying normal macrophage function and variant macrophages with alterations in function will provide models for diseases characterized by a deficient immune response and structural or biochemical lesions in the macrophage.